Figure 7.

Schematic diagram of the role of Piezo1 in innate lung immunity and pulmonary fibrosis. Periodic hydrostatic pressure in the lungs can activate monocyte Piezo1 to cause Ca²⁺ influx, phosphorylation of transcription factor cJun, and expression of endothelin 1 (ET1), which in turn activates HIF1α via the endothelin receptor type B (EDNRB), Thereby promoting the transcription of pro-inflammatory mediator programs. Piezo1 also increased the secretion of the chemokine CXCL2 in monocytes in the lung, inducing neutrophils to migrate from the blood vessels to the lungs to clear bacteria. Piezo1 senses alveolar tone and is involved in the secretion of alveolar surfactant and proliferation of ATII. Alveolar hyperextension leads to reduced secretion of alveolar surfactant and apoptosis of ATII, exacerbating lung injury and inflammation in ARDS patients. Piezo1 upregulation in alveoli induces an epithelial-mesenchymal transition with increased extracellular matrix (ECM) stiffness and promotes pulmonary fibrosis.